Isolated preparations of alpha-l-antitrypsin (alpha-lAT), trace-labeled with radioiodine, have been used to obtain data on the turnover of alpha-1AT in normal subjects and patients with alpha-1AT deficiency who have either pulmonary emphysema or chronic hepatocellular disease. The protease inhibitor (Pi) phenotypes of subjects donating plasma for isolation of alpha-lAT and subjects undergoing alpha-lAT turnover studies have been determined. The fractional catabolic rates of M alpha-lAT from normal subjects (phenotype PiMM) and Z alpha-lAT from patients with alpha-lAT deficiency (phenotype PiZZ) are similar in both normal subjects and patients with alpha-lAT deficiency. These findings imply that the low serum alpha-lAT concentration in alpha-lAT deficiency is due to impaired hepatic release of alpha-lAT and that the differences in molecular structure between the Z and M proteins have little effect on the catabolism of alpha-lAT. In common with other glycoproteins, desialylated (i.e. neuraminidase-treated) alpha-lAT is rapidly cleared from plasma by the liver. Pi phenotypes have been determined in populations of patients with rheumatoid arthritis, systemic lupus erythematosis and Sjogren's syndrome.